Knowing the enemy: strategic targeting of complement to treat Alzheimer disease

Nature Reviews Neurology, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Язык: Английский

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Brain-penetrant complement inhibition mitigates neurodegeneration in an Alzheimer's disease mouse model

Brain, Год журнала: 2024, Номер unknown

Опубликована: Авг. 29, 2024

Abstract Complement activation is implicated in driving brain inflammation, self-cell damage and progression of injury Alzheimer's disease other neurodegenerative diseases. Here, we investigate the impact delivery a complement-blocking antibody on neurodegeneration an mouse model. We engineered brain-penetrant recombinant targeting pro-inflammatory membrane attack complex. Systemic administration this APPNL-G-F mice reduced levels complement products, demonstrating successful entry target engagement. Prolonged treatment decreased synapse loss, amyloid burden inflammatory cytokine levels, concomitant with cognitive improvement compared to controls. These results underscore potential complement-inhibiting drugs as promising therapeutics, downstream plaques disease.

Язык: Английский

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The schizophrenia-associated gene CSMD1 encodes a complement classical pathway inhibitor predominantly expressed by astrocytes and at synapses in mice and humans

Brain Behavior and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Involvement of Complement in Alzheimer’s Disease: From Genetics Through Pathology to Therapeutic Strategies

Current topics in behavioral neurosciences, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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